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Identification of the potential gene regulatory networks and therapeutics in aged mice with postoperative neurocognitive disorder

ABSTRACT: Identification of the potential gene regulatory networks and therapeutics in aged mice with postoperative neurocognitive disorder

PROVIDER: PRJNA729766 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14525660.fastq.gz	Fastqsanger.gz
	SRR14525661.fastq.gz	Fastqsanger.gz
	SRR14525662.fastq.gz	Fastqsanger.gz
	SRR14525663.fastq.gz	Fastqsanger.gz
	SRR14525664.fastq.gz	Fastqsanger.gz

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Identification of the potential gene regulatory networks and therapeutics in aged mice with postoperative neurocognitive disorder (mRNA)

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Project description:Elderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.

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Identification of the potential gene regulatory networks and therapeutics in aged mice with postoperative neurocognitive disorder

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Identification of the Potential Gene Regulatory Networks and Therapeutics in Aged Mice With Postoperative Neurocognitive Disorder.

Project description:Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients, characterized by mental disorder, anxiety, personality changes, and impaired memory. At present, the molecular mechanism of PND remains largely unclear, and the ideal biomarker for clinical diagnosis and prognosis are lacking. Circular RNA (circRNA) and microRNA (miRNA), as unique non-coding RNAs, affecting the regulation of miRNAs on genes and further intervening in the progression of diseases through the sponge action between the two. Besides, it could be served as novel biomarkers in various diseases. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs, and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs, and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR. Bioinformatics analysis results suggested that neuroinflammation was the main pathological mechanism of PND. The construction of competitive endogenous RNA (ceRNA) networks and the identification of hub genes provided possible therapeutic targets for PND. Cinnarizine and Clemastine were predicted to have the potential therapeutic effects on PND. This is the first study to explore the differential expression profiles of genes and their regulation mechanisms in PND, our results provided new clues and targets for the treatment of this refractory disease.

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